madman
Super Moderator
* Gaps in long-term data and areas for further research are identified, underscoring the need for careful application in clinical practice. This paper emphasises a multidisciplinary approach in patient selection, rigorous monitoring protocols, and fully informed decision-making. By presenting a comprehensive review of the evidence, we aim to clarify the role of TRT in improving quality of life for men in remission from prostate cancer, while ensuring that oncological safety remains the highest priority.
Abstract
Hypogonadism in men with a history of prostate cancer presents a complex clinical challenge, with longstanding concerns that testosterone replacement therapy (TRT) could potentially stimulate cancer recurrence or progression. This paper provides an up-to-date review of the evidence on the safety and efficacy of TRT, focusing on its use in key clinical scenarios such as active surveillance, post-radical prostatectomy, and post-radiotherapy. We examine the latest data on oncological safety, including risks of disease progression and biochemical recurrence, alongside the benefits of TRT in addressing hypogonadal symptoms such as fatigue, mood disturbance, and sexual dysfunction. The discussion also considers how TRT safety aligns with advancements in prostate cancer biology, including the saturation model, and how these insights are reflected in guidelines from major organizations such as the British Society for Sexual Medicine (BSSM), American Urological Association (AUA), and European Association of Urology (EAU). Gaps in long-term data and areas for further research are identified, underscoring the need for careful application in clinical practice. This paper emphasises a multidisciplinary approach in patient selection, rigorous monitoring protocols, and fully informed decision-making. By presenting a comprehensive review of the evidence, we aim to clarify the role of TRT in improving quality of life for men in remission from prostate cancer, while ensuring that oncological safety remains the highest priority.
Introduction
Testosterone replacement therapy (TRT) has long been a subject of debate in men with a history of prostate cancer due to concerns that testosterone may stimulate tumor growth. However, a growing body of evidence suggests that TRT, when carefully administered to appropriately selected patients, may be both safe and offer significant benefits.
This document serves as a consensus guideline for the British Society for Sexual Medicine (BSSM) on the use of TRT in symptomatic hypogonadal men in remission from prostate cancer. It is informed by the latest research, clinical guidelines, and expert insights, providing healthcare professionals with a comprehensive understanding of the risks, benefits, and current gaps in knowledge surrounding TRT. The aim is to offer evidence-based guidance to support informed decision-making and enhance quality of life for patients through symptom relief, while maintaining rigorous monitoring to ensure oncological safety. Decisions regarding the use of TRT in this population should, wherever possible, be made in a multidisciplinary team (MDT) setting to ensure a thorough evaluation of individual patient risks and benefits.
Current Guidelines
TRT is increasingly recognized as a safe option for appropriately selected men with a history of prostate cancer, aligning with guidelines from major professional organizations. The BSSM assert that there is no compelling evidence linking TRT to the initiation or promotion of prostate cancer [1, 2, 3]. Similarly, the American Urological Association (AUA) [4] and European Association of Urology (EAU) support the cautious use of TRT in hypogonadal men with a history of prostate cancer who are disease-free, provided certain criteria are met. Key points from these guidelines are included in Table 1 [1, 2, 3, 4, 5, 6].
Current guidelines reflect significant progress in recognizing the safety of TRT for men with a history of prostate cancer. These guidelines affirm that TRT can be offered to symptomatic hypogonadal men who are disease-free following treatment for low-risk prostate cancer, provided they meet certain criteria.
Emerging evidence suggests that, with appropriate caution and robust monitoring, TRT could potentially be extended to a broader group of patients without compromising oncological safety. Studies consistently underline the benefits of TRT in improving survivorship by alleviating hypogonadal symptoms such as fatigue, low mood, and diminished sexual function, thereby enhancing overall quality of life.
This document outlines the rationale for offering TRT to men in remission who had low-risk prostate cancer prior to treatment, in line with a consensus approach from the BSSM. The approach is rooted in a commitment to fully informed decision-making, careful patient selection, and rigorous monitoring. Our goal is to offer symptomatic relief through TRT while ensuring the highest standards of safety and care.
1. Why TRT was historically considered risky
2. The saturation model
The model has gained significant traction for its ability to explain the limited impact of testosterone beyond the saturation point, but several critiques remain. Prostate cancer’s heterogeneity suggests that high-risk or advanced subtypes with AR overexpression or mutations may not conform to the model. The model primarily addresses low- to intermediate-risk disease, with limited applicability to advanced or metastatic prostate cancer. Variability in AR sensitivity among individuals raises questions about the generalizability of the model.
MODERN RESEARCH AND RISK ASSESSMENT OF TRT BY PATIENT GROUP
1. Men with no history of prostate cancer
1) TRT in men with potential precursors
2. Men with prostate cancer
1) Men on active surveillance
Summary
Current evidence suggests that TRT may be safely administered to hypogonadal men on AS for prostate cancer, with consistently no indication of increased disease progression or the need for definitive treatment across existing studies. However, the data remains limited, with small sample sizes, short follow-up periods, and a lack of robust prospective trials. These findings, while encouraging, depend heavily on careful patient selection, frequent PSA monitoring, MRIs, and biopsies to detect early signs of progression. Observational and retrospective studies provide valuable insights but need further validation from well-designed prospective research. Theoretical models such as the saturation model offer a plausible biological basis for these findings, supporting the cautious use of TRT within structured AS protocols. Nonetheless, clinicians should approach TRT in this population with care, acknowledging the need for more comprehensive data to confirm long-term safety.
Summary
Current evidence suggests that TRT is oncologically safe for hypogonadal men following RP, with no significant increases in BCR rates and PSA levels remaining within acceptable ranges across studies. In low- to intermediate-risk patients, the data is reassuring, supporting TRT as a viable option to improve quality of life, including energy, libido, and erectile function. For high-risk patients, some small studies have even shown reduced BCR rates, suggesting potential benefits; however, these findings are limited by very small patient numbers, a lack of robust data, and currently fall outside clinical guidelines. This highlights a critical need for further research to address these gaps in understanding. Increased monitoring remains essential for all patient groups to ensure safety.
3) Men after radiotherapy
Summary
Evidence increasingly supports TRT as a safe and effective option for hypogonadal men postradiotherapy for prostate cancer, with studies showing stable PSA levels and no significant rise in recurrence rates. TRT also improves energy, mood, and sexual function, enhancing quality of life for symptomatic men. However, some studies indicate a slightly higher risk of BCR in men treated with radiotherapy on TRT compared to those who undergo surgery, likely due to the presence of residual prostatic tissue. This underscores the importance of careful, individualized patient selection, limiting TRT to men who are symptomatic and initiating treatment only after achieving a stable PSA nadir. Pre-treatment testosterone levels could also play a vital role in prehabilitation, optimizing overall health and readiness for therapy. Robust monitoring, including regular PSA assessments, remains essential to ensure oncological safety and to promptly identify any early signs of disease progression. MDT input from oncologists, endocrinologists, and urologists is particularly valuable in complex cases, supporting safe, individualized treatment plans. Larger, long-term studies are needed to confirm these findings and further refine the safety profile of TRT in this population.
CARDIOVASCULAR CONCERNS VS BENEFITS
Summary
The cardiovascular effects of TRT have been a topic of considerable debate. Early studies which initially raised the concerns about increased cardiovascular risks, were so significantly flawed in their methodology they cannot be deemed reliable. In contrast, the TRAVERSE trial, a large and well-designed RCT, has provided strong evidence that TRT does not significantly increase the risk of MACE, even in men with pre-existing cardiovascular conditions. Nonetheless, potential risks, such as pulmonary embolism, require careful consideration. On the other hand, TRT may offer cardiovascular benefits by improving metabolic and endothelial dysfunction associated with low testosterone, potentially mitigating cardiovascular risk factors. Clinicians should adopt a personalized approach, carefully balancing the potential risks and benefits of TRT for each individual patient. When appropriate, TRT should be integrated with lifestyle modifications and PDE5Is to enhance overall outcomes and provide a comprehensive strategy for symptom management.
OTHER CONSIDERATIONS
1. Bipolar Androgen Therapy
Although this is not the target population for this BSSM consensus, the TRANSFORMER trial highlights that testosterone’s impact on prostate cancer is highly context dependent. The ability to use testosterone therapeutically in men with advanced prostate cancer challenges the notion that TRT is inherently unsafe in men without active disease. Previous blanket contraindications for TRT in men with a history of prostate cancer may therefore have been overly cautious, particularly for those with no residual disease who experience significant quality-of-life impairments due to hypogonadism.
While these findings are specific to the mCRPC setting and cannot be directly applied to earlier-stage disease, they provide valuable mechanistic insights into androgen dynamics. These insights support the need for a more nuanced approach to TRT in earlier-stage prostate cancer, guided by patient-specific factors and disease context. Vigilance and individualized risk assessment remain crucial to ensuring safety and efficacy for patients.
Conclusions
The use of TRT in men with a history of prostate cancer must be considered on a case-by-case basis. Modern evidence, in contrast to historical concerns, supports its use in appropriately selected patients. For men with low- to intermediate-risk prostate cancer, multiple studies indicate that TRT is a safe and effective option, providing significant benefits without increasing the risk of cancer recurrence. The positive effects on quality of life, such as improvements in sexual function, energy levels and mood, suggest that symptomatic hypogonadal patients could derive substantial benefit from TRT and should be offered this treatment choice, provided they are fully informed of the potential risks and benefits. In contrast, for high-risk patients, the long-term safety of TRT remains unclear, and more caution is warranted. Further research is needed to better understand its impact in this group.
Ultimately, TRT offers an important treatment option for hypogonadal men with a history of prostate cancer, but patient selection and regular monitoring are essential to ensure safety. Decisions regarding TRT should be made, wherever feasible, in an MDT setting to ensure comprehensive evaluation of all relevant factors, including oncological risks, cardiovascular health, and patient-specific priorities. The decision to initiate TRT should be guided by a personalized approach, considering the patient’s individual wishes, health history, cancer risk, and quality of life considerations.
Abstract
Hypogonadism in men with a history of prostate cancer presents a complex clinical challenge, with longstanding concerns that testosterone replacement therapy (TRT) could potentially stimulate cancer recurrence or progression. This paper provides an up-to-date review of the evidence on the safety and efficacy of TRT, focusing on its use in key clinical scenarios such as active surveillance, post-radical prostatectomy, and post-radiotherapy. We examine the latest data on oncological safety, including risks of disease progression and biochemical recurrence, alongside the benefits of TRT in addressing hypogonadal symptoms such as fatigue, mood disturbance, and sexual dysfunction. The discussion also considers how TRT safety aligns with advancements in prostate cancer biology, including the saturation model, and how these insights are reflected in guidelines from major organizations such as the British Society for Sexual Medicine (BSSM), American Urological Association (AUA), and European Association of Urology (EAU). Gaps in long-term data and areas for further research are identified, underscoring the need for careful application in clinical practice. This paper emphasises a multidisciplinary approach in patient selection, rigorous monitoring protocols, and fully informed decision-making. By presenting a comprehensive review of the evidence, we aim to clarify the role of TRT in improving quality of life for men in remission from prostate cancer, while ensuring that oncological safety remains the highest priority.
Introduction
Testosterone replacement therapy (TRT) has long been a subject of debate in men with a history of prostate cancer due to concerns that testosterone may stimulate tumor growth. However, a growing body of evidence suggests that TRT, when carefully administered to appropriately selected patients, may be both safe and offer significant benefits.
This document serves as a consensus guideline for the British Society for Sexual Medicine (BSSM) on the use of TRT in symptomatic hypogonadal men in remission from prostate cancer. It is informed by the latest research, clinical guidelines, and expert insights, providing healthcare professionals with a comprehensive understanding of the risks, benefits, and current gaps in knowledge surrounding TRT. The aim is to offer evidence-based guidance to support informed decision-making and enhance quality of life for patients through symptom relief, while maintaining rigorous monitoring to ensure oncological safety. Decisions regarding the use of TRT in this population should, wherever possible, be made in a multidisciplinary team (MDT) setting to ensure a thorough evaluation of individual patient risks and benefits.
Current Guidelines
TRT is increasingly recognized as a safe option for appropriately selected men with a history of prostate cancer, aligning with guidelines from major professional organizations. The BSSM assert that there is no compelling evidence linking TRT to the initiation or promotion of prostate cancer [1, 2, 3]. Similarly, the American Urological Association (AUA) [4] and European Association of Urology (EAU) support the cautious use of TRT in hypogonadal men with a history of prostate cancer who are disease-free, provided certain criteria are met. Key points from these guidelines are included in Table 1 [1, 2, 3, 4, 5, 6].
Current guidelines reflect significant progress in recognizing the safety of TRT for men with a history of prostate cancer. These guidelines affirm that TRT can be offered to symptomatic hypogonadal men who are disease-free following treatment for low-risk prostate cancer, provided they meet certain criteria.
Emerging evidence suggests that, with appropriate caution and robust monitoring, TRT could potentially be extended to a broader group of patients without compromising oncological safety. Studies consistently underline the benefits of TRT in improving survivorship by alleviating hypogonadal symptoms such as fatigue, low mood, and diminished sexual function, thereby enhancing overall quality of life.
This document outlines the rationale for offering TRT to men in remission who had low-risk prostate cancer prior to treatment, in line with a consensus approach from the BSSM. The approach is rooted in a commitment to fully informed decision-making, careful patient selection, and rigorous monitoring. Our goal is to offer symptomatic relief through TRT while ensuring the highest standards of safety and care.
BACKGROUND1. Why TRT was historically considered risky
2. The saturation model
The model has gained significant traction for its ability to explain the limited impact of testosterone beyond the saturation point, but several critiques remain. Prostate cancer’s heterogeneity suggests that high-risk or advanced subtypes with AR overexpression or mutations may not conform to the model. The model primarily addresses low- to intermediate-risk disease, with limited applicability to advanced or metastatic prostate cancer. Variability in AR sensitivity among individuals raises questions about the generalizability of the model.
MODERN RESEARCH AND RISK ASSESSMENT OF TRT BY PATIENT GROUP
1. Men with no history of prostate cancer
1) TRT in men with potential precursors
2. Men with prostate cancer
1) Men on active surveillance
Summary
Current evidence suggests that TRT may be safely administered to hypogonadal men on AS for prostate cancer, with consistently no indication of increased disease progression or the need for definitive treatment across existing studies. However, the data remains limited, with small sample sizes, short follow-up periods, and a lack of robust prospective trials. These findings, while encouraging, depend heavily on careful patient selection, frequent PSA monitoring, MRIs, and biopsies to detect early signs of progression. Observational and retrospective studies provide valuable insights but need further validation from well-designed prospective research. Theoretical models such as the saturation model offer a plausible biological basis for these findings, supporting the cautious use of TRT within structured AS protocols. Nonetheless, clinicians should approach TRT in this population with care, acknowledging the need for more comprehensive data to confirm long-term safety.
2) Men after radical prostatectomySummary
Current evidence suggests that TRT is oncologically safe for hypogonadal men following RP, with no significant increases in BCR rates and PSA levels remaining within acceptable ranges across studies. In low- to intermediate-risk patients, the data is reassuring, supporting TRT as a viable option to improve quality of life, including energy, libido, and erectile function. For high-risk patients, some small studies have even shown reduced BCR rates, suggesting potential benefits; however, these findings are limited by very small patient numbers, a lack of robust data, and currently fall outside clinical guidelines. This highlights a critical need for further research to address these gaps in understanding. Increased monitoring remains essential for all patient groups to ensure safety.
3) Men after radiotherapy
Summary
Evidence increasingly supports TRT as a safe and effective option for hypogonadal men postradiotherapy for prostate cancer, with studies showing stable PSA levels and no significant rise in recurrence rates. TRT also improves energy, mood, and sexual function, enhancing quality of life for symptomatic men. However, some studies indicate a slightly higher risk of BCR in men treated with radiotherapy on TRT compared to those who undergo surgery, likely due to the presence of residual prostatic tissue. This underscores the importance of careful, individualized patient selection, limiting TRT to men who are symptomatic and initiating treatment only after achieving a stable PSA nadir. Pre-treatment testosterone levels could also play a vital role in prehabilitation, optimizing overall health and readiness for therapy. Robust monitoring, including regular PSA assessments, remains essential to ensure oncological safety and to promptly identify any early signs of disease progression. MDT input from oncologists, endocrinologists, and urologists is particularly valuable in complex cases, supporting safe, individualized treatment plans. Larger, long-term studies are needed to confirm these findings and further refine the safety profile of TRT in this population.
CARDIOVASCULAR CONCERNS VS BENEFITS
Summary
The cardiovascular effects of TRT have been a topic of considerable debate. Early studies which initially raised the concerns about increased cardiovascular risks, were so significantly flawed in their methodology they cannot be deemed reliable. In contrast, the TRAVERSE trial, a large and well-designed RCT, has provided strong evidence that TRT does not significantly increase the risk of MACE, even in men with pre-existing cardiovascular conditions. Nonetheless, potential risks, such as pulmonary embolism, require careful consideration. On the other hand, TRT may offer cardiovascular benefits by improving metabolic and endothelial dysfunction associated with low testosterone, potentially mitigating cardiovascular risk factors. Clinicians should adopt a personalized approach, carefully balancing the potential risks and benefits of TRT for each individual patient. When appropriate, TRT should be integrated with lifestyle modifications and PDE5Is to enhance overall outcomes and provide a comprehensive strategy for symptom management.
OTHER CONSIDERATIONS
1. Bipolar Androgen Therapy
Although this is not the target population for this BSSM consensus, the TRANSFORMER trial highlights that testosterone’s impact on prostate cancer is highly context dependent. The ability to use testosterone therapeutically in men with advanced prostate cancer challenges the notion that TRT is inherently unsafe in men without active disease. Previous blanket contraindications for TRT in men with a history of prostate cancer may therefore have been overly cautious, particularly for those with no residual disease who experience significant quality-of-life impairments due to hypogonadism.
While these findings are specific to the mCRPC setting and cannot be directly applied to earlier-stage disease, they provide valuable mechanistic insights into androgen dynamics. These insights support the need for a more nuanced approach to TRT in earlier-stage prostate cancer, guided by patient-specific factors and disease context. Vigilance and individualized risk assessment remain crucial to ensuring safety and efficacy for patients.
Conclusions
The use of TRT in men with a history of prostate cancer must be considered on a case-by-case basis. Modern evidence, in contrast to historical concerns, supports its use in appropriately selected patients. For men with low- to intermediate-risk prostate cancer, multiple studies indicate that TRT is a safe and effective option, providing significant benefits without increasing the risk of cancer recurrence. The positive effects on quality of life, such as improvements in sexual function, energy levels and mood, suggest that symptomatic hypogonadal patients could derive substantial benefit from TRT and should be offered this treatment choice, provided they are fully informed of the potential risks and benefits. In contrast, for high-risk patients, the long-term safety of TRT remains unclear, and more caution is warranted. Further research is needed to better understand its impact in this group.
Ultimately, TRT offers an important treatment option for hypogonadal men with a history of prostate cancer, but patient selection and regular monitoring are essential to ensure safety. Decisions regarding TRT should be made, wherever feasible, in an MDT setting to ensure comprehensive evaluation of all relevant factors, including oncological risks, cardiovascular health, and patient-specific priorities. The decision to initiate TRT should be guided by a personalized approach, considering the patient’s individual wishes, health history, cancer risk, and quality of life considerations.
